Mechanisms of Blood–Brain Barrier Dysfunction in Traumatic Brain Injury

International Journal of Molecular Sciences, Journal Year: 2020, Volume and Issue: 21(9), P. 3344 - 3344

Published: May 8, 2020

Traumatic brain injuries (TBIs) account for the majority of injury-related deaths in United States with roughly two million TBIs occurring annually. Due to spectrum severity and heterogeneity TBIs, investigation into secondary injury is necessary order formulate an effective treatment. A mechanical consequence trauma involves dysregulation blood–brain barrier (BBB) which contributes exposure peripheral components parenchyma. Recent studies have shed light on mechanisms BBB breakdown TBI including novel intracellular signaling cell–cell interactions within niche. The current review provides overview BBB, detection methods disruption, cellular molecular implicated regulating its stability following TBI.

Language: Английский

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Targeting Neuroinflammation to Treat Alzheimer’s Disease

CNS Drugs, Journal Year: 2017, Volume and Issue: 31(12), P. 1057 - 1082

Published: Dec. 1, 2017

Over the past few decades, research on Alzheimer's disease (AD) has focused pathomechanisms linked to two of major pathological hallmarks extracellular deposition beta-amyloid peptides and intra-neuronal formation neurofibrils. Recently, a third component, neuroinflammatory reaction mediated by cerebral innate immune cells, entered spotlight, prompted findings from genetic, pre-clinical, clinical studies. Various proteins that arise during neurodegeneration, including beta-amyloid, tau, heat shock proteins, chromogranin, among others, act as danger-associated molecular patterns, that—upon engagement pattern recognition receptors—induce inflammatory signaling pathways ultimately lead production release mediators. These may have beneficial effects but compromise neuronal function cause cell death. The current review, assembled participants Chiclana Summer School Neuroinflammation 2016, provides an overview our understanding AD-related processes. We describe principal cellular players in inflammation they pertain AD, examine modifying factors, discuss potential future therapeutic targets.

Language: Английский

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Targeting pericytes for therapeutic approaches to neurological disorders

Acta Neuropathologica, Journal Year: 2018, Volume and Issue: 136(4), P. 507 - 523

Published: Aug. 10, 2018

Many central nervous system diseases currently lack effective treatment and are often associated with defects in microvascular function, including a failure to match the energy supplied by blood used on neuronal computation, or breakdown of blood–brain barrier. Pericytes, an under-studied cell type located capillaries, crucial importance regulating diverse functions, such as angiogenesis, barrier, capillary flow movement immune cells into brain. They also form part "glial" scar isolating damaged parts CNS, may have stem cell-like properties. Recent studies suggested that pericytes play role neurological diseases, thus therapeutic target disorders stroke, traumatic brain injury, migraine, epilepsy, spinal cord diabetes, Huntington's disease, Alzheimer's multiple sclerosis, glioma, radiation necrosis amyotrophic lateral sclerosis. Here we report recent advances our understanding pericyte biology discuss how could be targeted develop novel approaches disorders, increasing flow, preserving barrier entry modulating formation vessels in, glial around, regions.

Language: Английский

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Markers for human brain pericytes and smooth muscle cells

Journal of Chemical Neuroanatomy, Journal Year: 2018, Volume and Issue: 92, P. 48 - 60

Published: June 7, 2018

Language: Английский

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Development and Function of the Blood-Brain Barrier in the Context of Metabolic Control

Frontiers in Neuroscience, Journal Year: 2017, Volume and Issue: 11

Published: April 21, 2017

Under physiological conditions, the brain consumes over 20% of whole body energy supply. The blood-brain barrier (BBB) allows dynamic interactions between blood capillaries and neuronal network in order to provide an adequate control molecules that are transported out brain. Alterations BBB structure function affecting accessibility nutrients exit toxins found a number diseases, which turn may disturb nutrient signaling. In this review we explore major advances obtained understanding development how its impacts on function. Furthermore, focus particularities permeability hypothalamus, role metabolic potential impact hypothalamic abnormities related diseases.

Language: Английский

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Brain Microvascular Pericytes in Vascular Cognitive Impairment and Dementia

Frontiers in Aging Neuroscience, Journal Year: 2020, Volume and Issue: 12

Published: April 14, 2020

Pericytes are unique, multi-functional mural cells localized at the abluminal side of perivascular space in microvessels. Originally discovered nineteenth century, pericytes had drawn less attention until decades ago mainly due to lack specific markers. Recently, however, a growing body evidence has revealed that play various important roles: development and maintenance blood-brain barrier (BBB), regulation neurovascular system (e.g., vascular stability, vessel formation, cerebral blood flow, etc.), trafficking inflammatory cells, clearance toxic waste products from brain, acquisition stem cell-like properties. In unit, perform these functions through coordinated crosstalk with neighboring including endothelial, glial, neuronal cells. Dysfunction contribute wide variety diseases lead cognitive impairments such as small disease (SVD), acute stroke, Alzheimer’s (AD), other neurological disorders. For instance, SVDs, pericyte degeneration leads microvessel instability demyelination while constriction after ischemia causes no-reflow phenomenon brain capillaries. AD, which shares some common risk factors dementia, reduction coverage subsequent microvascular observed association white matter attenuation impaired cognition. Pericyte loss BBB-breakdown, stagnates amyloid β leakage neurotoxic molecules into parenchyma. this review, we first summarize characteristics pericytes, their roles central nervous system. Then, focus on how dysfunctional pathogenesis impairment ‘small vessel’ ‘large diseases, well AD. Finally, discuss therapeutic implications for disorders by targeting pericytes.

Language: Английский

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The energetic brain – A review from students to students

Journal of Neurochemistry, Journal Year: 2019, Volume and Issue: 151(2), P. 139 - 165

Published: July 18, 2019

Abstract The past 20 years have resulted in unprecedented progress understanding brain energy metabolism and its role health disease. In this review, which was initiated at the 14th International Society for Neurochemistry Advanced School, we address basic concepts of approach question why has high expenditure. Our review illustrates that vertebrate a need because number neurons to maintain delicate interplay between metabolism, neurotransmission, plasticity. Disturbances energetic balance, mitochondria quality control or glia–neuron metabolic interaction may lead circuit malfunction even severe disorders CNS . We cover neuronal consumption neural transmission (‘housekeeping’) cellular processes. Additionally, describe most common (glucose) alternative sources namely glutamate, lactate, ketone bodies, medium chain fatty acids. discuss multifaceted non‐neuronal cells transport substrates from circulation (pericytes astrocytes) supply (astrocytes microglia) usage different fuels. Finally, pathological consequences disrupted homeostasis image

Language: Английский

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PDGFRβ Cells Rapidly Relay Inflammatory Signal from the Circulatory System to Neurons via Chemokine CCL2

Neuron, Journal Year: 2018, Volume and Issue: 100(1), P. 183 - 200.e8

Published: Sept. 27, 2018

Language: Английский

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Cytokines in CAR T Cell–Associated Neurotoxicity

Frontiers in Immunology, Journal Year: 2020, Volume and Issue: 11

Published: Dec. 16, 2020

Chimeric antigen receptor (CAR) T cells provide new therapeutic options for patients with relapsed/refractory hematologic malignancies. However, neurotoxicity is a frequent, and potentially fatal, complication. The spectrum of manifestations ranges from delirium language dysfunction to seizures, coma, fatal cerebral edema. This novel syndrome has been designated immune effector cell-associated (ICANS). In this review, we draw an arc our current understanding how systemic local cytokine release act on the CNS, toward possible preventive approaches. We systematically review reported correlations secreted inflammatory mediators in serum/plasma cerebrospinal fluid risk ICANS receiving CAR cell therapy. Possible pathophysiologic impacts CNS are covered detail most promising candidate cytokines, including IL-1, IL-6, IL-15, GM-CSF. To insight into final common pathways inflammation, place context other conditions that associated neurologic dysfunction, sepsis-associated encephalopathy, malaria, thrombotic microangiopathy, infections, hepatic encephalopathy. then what known about interaction components neurovascular unit, endothelial cells, pericytes, astrocytes, microglia neurons respond challenges. Current approaches, corticosteroids blockade IL-1 IL-6 signaling, reviewed role cytokines ICANS. Throughout, point out gaps knowledge approaches investigation mechanism, prevention, treatment

Language: Английский

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A case report of clonal EBV-like memory CD4+ T cell activation in fatal checkpoint inhibitor-induced encephalitis

Nature Medicine, Journal Year: 2019, Volume and Issue: 25(8), P. 1243 - 1250

Published: July 22, 2019

Language: Английский

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